title: A therapeutic cancer vaccine targeting carcinoembryonic antigen in intestinal carcinomas.
abstract: A genetic vaccine platform based on DNA electroporation (DNA-EP) and adenovirus (Ad) was used to generate immune response against human carcinoembryonic antigen (CEA) and antitumor effects in murine models with spontaneous tumors arising in an orthotopic location. CEA transgenic (CEA.Tg) mice treated with the carcinogen 1,2-dimethylhydrazine developed CEA-overexpressing tumors that resembled human sporadic colorectal cancer. APC1638N/CEA hybrid mice, generated by crossing mice carrying the adenomatous polyposis coli (Apc1638N) gene mutation with CEA.Tg mice, are representative of human familial polyposis and develop polyps that overexpress the antigen. In both models, the DNA-EP/Ad vaccine succeeded in breaking immune tolerance and achieved significant antitumor effects in therapeutic settings. Our data suggest that genetic vaccines targeting CEA may be feasible strategies against gut tumors that overexpress the antigen. In addition, these models are powerful systems for evaluating antigen-specific tumor immunity and assessing therapeutic vaccine strategies for human colorectal cancer.
authors.affiliation: Department of Oncology, Istituto di Ricerche di Biologia Molecolare (IRBM), Merck Research Laboratories, Pomezia (Rome), Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mori
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannetti
authors.forename: Daniela
authors.initials: D
authors.lastname: Peruzzi
authors.forename: Domenico
authors.initials: D
authors.lastname: Lazzaro
authors.forename: Saverio
authors.initials: S
authors.lastname: Giampaoli
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Nicola
authors.initials: N
authors.lastname: La Monica
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
mesh_terms: D018256:Adenomatous Polyps / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D012015:Reference Standards; D015854:Up-Regulation
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen